This invention relates to a test system and a procedure, using coupled enzyme systems and having an extended range of measurements, for the determination of substances in liquids, in particular in body fluids.
The determination of substances in body fluids is of great importance for medical diagnosis. This applies not only to quantitative determinations, but also to semiquantitative or qualitative procedures which permit self-monitoring of the individual patient or simple screening. As is appropriate for the importance of these tests, a large number of procedures have been disclosed. The most frequently used procedures are enzymic methods of determination which permit a high degree of specificity. In such methods, the increase or decrease of a reactant participating in the determination reaction is indirectly or directly determined visually, photometrically or using other optical or physicochemical procedures. Common to all these systems is that always only one enzyme or enzyme system reacts with the substance to be determined, whereupon, in an identical or proportional molar ratio, a reaction product is formed or a participant in the reaction is consumed. As a consequence, the range of measurement is approximately equal in size for all procedures, and it can be displaced in accordance with the sensitivity of the measurement signal and the sample dilution.
Tests are necessary for medical diagnosis which are able not only reliably to determine only slightly differing values in the boundary zone between the normal range and the pathological range, but also, at the same time, to cover as wide a range as possible in the pathological range. This also applies, in particular, to screening methods, for example, with test strip systems. The range of measurement achieved with the conventional tests is inadequate for the requirements of some applications. This is particularly true for the determination of glucose. Attempts have already been made to solve this problem by using additives in the tests which change their sensitivity but a wider range of measurement has been achieved heretofore only by using a combination of several tests, each having a range of measurement which is adjusted to be appropriately different from the others.